DESCRIPTION (applicant's abstract): Most individuals who suffer from sleep disorders experience involuntary loss of sleep due to fragmentation, inability to initiate or sustain sleep. However, lifestyle and work demands require millions of Americans without known sleep disorders to have shortened sleep amounts for prolonged periods of time. We hypothesize that sleep loss leads to an activation of the autonomic nervous system associated with stress that, when prolonged, results in impaired immune function. Until recently, the effects of chronic sleep restriction were completely unknown. We now know that neurobehavioral output is severely compromised by only 10 days of sleeping half the normal daily amount; but we know nothing about the effects of neuroendocrine, neuroimmune responses to an immune challenge. The proposed double-blind, placebo-controlled study will assess the effects of chronic sleep restriction on human host response to an experimental challenge with low dose endotoxin, cleaved from Escherichia-coli (E-coli). This research design will enable us to investigate not only the functioning of the early immune system with respect to host response to challenge during ongoing sleep restriction, but will allow us to examine longitudinal changes in circadian and sleep-related neuroendocrine and neuroimmune output. In addition, we will examine the rate of change across days of sleep restriction in neurobehavioral output, brain electrical activity, indices of mood, and neuroendocrine and neuroimmune parameters in order to assess the relative vulnerability of these systems to chronic sleep restriction. This research will significantly enhance our understanding of the role of sleep in host protection and autonomic regulation, and have broad implications for health maintenance and illness prevention.